Regulation of macrophage-mediated suppression by purine nucleoside phosphorylase substrates.
Thymuses from dexamethasone-treated rats contain macrophage-like cells that completely suppress the proliferative response of thymocytes to concanavalin A. This macrophage-mediated suppression is abolished by low concentrations of purine nucleoside phosphorylase (PNP) substrates: deoxyguanosine (20 microM), guanosine (100 microM), and deoxyinosine (250 microM). Similar effects were observed when resident peritoneal macrophages were used. Deoxyguanosine regulates suppression by acting directly on macrophages. The mode of deoxyguanosine action on macrophages does not involve its phosphorylation and incorporation into deoxynucleotide pools. The significance of this regulation of macrophage-mediated suppression by PNP substrates to immune regulation in normals and in PNP-deficient patients is discussed.
D000818:Animals; D002450:Cell Communication; D003208:Concanavalin A / Q000494:pharmacology; D003848:Deoxyguanine Nucleotides / Q000378:metabolism; D003849:Deoxyguanosine / Q000378:metabolism / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007375:Interleukin-1; D008213:Lymphocyte Activation; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D008297:Male; D010430:Pentosyltransferases / Q000494:pharmacology*; D011506:Proteins / Q000378:metabolism / Q000494:pharmacology*; D011683:Purine-Nucleoside Phosphorylase / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013601:T-Lymphocytes / Q000276:immunology*
D003848:Deoxyguanine Nucleotides; D007166:Immunosuppressive Agents; D007375:Interleukin-1; D011506:Proteins; D003208:Concanavalin A; D003907:Dexamethasone; C029603:deoxyguanosine triphosphate; D010430:Pentosyltransferases; D011683:Purine-Nucleoside Phosphorylase; D003849:Deoxyguanosine